GnRH analog in nasal spray that temporarily shuts down sex hormone production. Used in endometriosis, central precocious puberty, and, in Spain, in ovarian stimulation for IVF.
FDA (US): Approved (1990, Synarel) for endometriosis (adults, 6 months) and central precocious puberty in children of both sexes.
EMA (EU): No centralized authorization. In Spain, authorized by the AEMPS (1996, Synarel) for endometriosis and for controlled ovarian stimulation before IVF.
Dose
Endometriosis: 400 µg/day (one 200 µg spray in the morning and another at night), up to 800 µg/day if menstruation persists; recommended duration 6 months. Central precocious puberty: 1,600 µg/day. IVF (Spain): 800 µg/day (FDA label; CIMA-AEMPS label).
Safety
Low-estrogen effects: hot flashes, headache, mood changes, lower sex drive, vaginal dryness, acne, and muscle aches; nasal irritation in ~10%. Over 6 months it reduces vertebral bone density (loss of ~3–9% depending on the technique, only partially recovered). Repeating the course without assessing the bone is not recommended. Contraindicated in pregnancy, breastfeeding, and undiagnosed vaginal bleeding. Requires a prescription and medical monitoring.
Interactions
If a nasal decongestant is needed, use it at least 2 hours after the dose. Avoid sneezing right after applying it.
Differences between women and men
In adults it is indicated only in women (endometriosis, IVF). Contraindicated in pregnancy and breastfeeding. The drop in estrogen causes bone density loss in women treated for 6 months. In precocious puberty it is used in girls and boys.
Effect by goal · level of evidence
Endometriosis lesions and pain
improvesHighRCT (AA)in people
Severe pain 40%→5–10%
Double-blind trial in 213 women with laparoscopy-confirmed endometriosis: 6 months of nasal nafarelin (400 or 800 µg/day) reduced the extent of disease in more than 80% of patients, the same as danazol. The proportion with severe pain fell from ~40% to 5–10%. Unlike danazol, it did not worsen cholesterol, but it caused more hot flashes and lower libido.
Mimics natural GnRH but in a continuous manner. After an initial stimulus, the pituitary gland stops responding and LH and FSH production falls. As a result, estrogen (or testosterone) drops, which reduces endometriosis lesions or halts early puberty. The effect is reversible when the drug is stopped.
What the evidence says
In people
Lesions and pain from endometriosis. Double-blind trial in 213 women with laparoscopically confirmed endometriosis: 6 months of intranasal nafarelin (400 or 800 µg/day) reduced the extent of disease in more than 80% of patients, the same as danazol. The proportion with severe pain fell from ~40% to 5–10%. Unlike danazol, it did not worsen cholesterol, but it caused more hot flashes and lower libido. PubMed 2963213